Over 100,000 people rupture the anterior cruciate ligament (ACL) of the knee each year. The current best treatment, replacement of the ligament with a graft of tendon, does not replace the complex architecture and biomechanics of the original ligament, and as many as 50% of patients will have signs of arthritis at only 7 years after surgery. Because of the clinical importance of this injury and the lack of an optimal treatment method, I have become increasingly interested in developing new approaches to ACL injuries, and have spent the last five years working to combine a career conducting basic investigations in ligament healing with clinical practice as an orthopaedic surgeon. During that time, I have published seven first-author peer reviewed publications, served as the principal investigator on three grants, won three national awards for ligament research, spoken at national conferences and served as a reviewer and book section editor. The specific aims of this career award are to gain independence in several specific cellular and molecular assays, scaffold manufacture, the use of in vivo animal models and statistical analysis through coursework, seminar attendance and training in well-established laboratories. The acquisition of these skills will enhance my ability to serve as an independent scientist by lessening my current dependence on collaborators in these areas. This research proposal focuses on developing a new method of treatment for ACL rupture: enhanced primary repair. This technique makes use of a provisional scaffold to supplement a primary ligament repair and encourage healing in the gap between the ends of the ruptured ACL. This procedure could potentially restore the architecture and biomechanics of the knee, while maintaining the proprioceptive function of the ACL, thus potentially decreasing the risk of post-operative instability and osteoarthritis. The first specific aim is to define the cell and tissue events in the ACL after injury and the changes in these events after placement of a bioadhesive scaffold in the ACL defect. In the second aim, in vitro assays will be conducted to define the composition of a provisional scaffold which best stimulates ACL cells to mimic the MCL healing process. In the third aim, the optimized scaffolds will be tested in an in vivo canine ACL non-union model. Information gained in each of these aims will serve to improve our understanding of mechanisms of ligament healing.